When peripheral blood monocytes are cultured in vitro they spontaneously develop a cytotoxic ability and will lyse a variety of target cells including red blood cell and tumor targets. The effect of various cancer chemotherapeutic agents, including L-phenylalanine mustard (L-PAM), cis-DDP; Adriamycin (ADR) and Actinomycin D (Act.D.) on this cytotoxic function was investigated. Using 51Cr-labeled chicken red cells (CRC) as targets, we found that L-PAM, ADR, and cis-DDP all enhanced monocyte-mediated cytotoxicity (MMC). While cis-DDP and ADR enhanced cytotoxicity by direct stimulation of the killer monocyte; L-PAM affect both the killer monocyte and the suppressor lymphocyte. By contrast Actinomycin D suppressed cytotoxic function. We would like to propose that chemotherapeutic agents may in addition to causing direct tumor cytotoxicity also enhance normal immune function and, therefore, aid in host tumor rejection.